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Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n = 19,723) with normal fet...

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Detalles Bibliográficos
Autores principales: Kildisiute, Gerda, Kholosy, Waleed M., Young, Matthew D., Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R., Pacyna, Clarissa N., Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M., Langenberg-Ververgaert, Karin P.S., Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C.P., Tas, Michelle L., Wijnen, Marc H.W.A., van Noesel, Max M., del Valle, Ignacio, Barone, Giuseppe, van der Linden, Reinier, Duncan, Catriona, Anderson, John, Achermann, John C., Haniffa, Muzlifah, Teichmann, Sarah A., Rampling, Dyanne, Sebire, Neil J., He, Xiaoling, de Krijger, Ronald R., Barker, Roger A., Meyer, Kerstin B., Bayraktar, Omer, Straathof, Karin, Molenaar, Jan J., Behjati, Sam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864567/
https://www.ncbi.nlm.nih.gov/pubmed/33547074
http://dx.doi.org/10.1126/sciadv.abd3311
Descripción
Sumario:Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n = 19,723) with normal fetal adrenal single-cell transcriptomes (n = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.